Studies in several species have shown that a number of visual phenomena are regulated by circadian mechanisms. For example, synaptic ribbons in photoreceptor terminals in larval zebrafish undergo dramatic diurnal alterations. The ribbons are very prominent during day, but are almost completely absent at night. The implications of this circadian driven process on visual function are not well understood. The proposed experiments are aimed at investigating how plasticity of synaptic ribbons in the eye relates to visual responsiveness in larval zebrafish. Preliminary studies show that larval fish at 5 days of age have normal electroretinograms (ERGs) during the day, but fail to respond to illumination at night. Two behavioral tests, the optokinetic response (OKR) and the visual-motor response (VMR), indicate that fluctuations in visual responsiveness in the day and night are not only profound in larval zebrafish, but that vision may be completely lost at night. In Specific Aim 1, I will determine how the changes in ERG and visual behavioral sensitivity alter as a function of time of day and light exposure in larval zebrafish. Single-unit and ERG recordings will be used to determine the changes in the functional properties of retinal cells in the inner and outer retina. The OKR and the VMR tests will be used to determine how time of day and light exposure affects visual responsiveness and behavior of zebrafish. In Specific Aim 2, I will characterize and quantitate changes in ribbon structure in the retina under physiological conditions as well as under various light and dark conditions. The structural changes of synaptic ribbons will be studied by electron microscopy or immunohistochemistry using antibodies against synaptic ribbon proteins. PUBLIC HEALTH RELEVANCE Zebrafish have emerged as a powerful model system to study processes underlying visual system development and differentiation. Ultrastructural analysis on larval zebrafish have shown that synaptic ribbons in photoreceptor terminals undergo structural changes over the course of the day and that this process is circadian driven. The implications of this circadian driven process on visual function are not well understood. Further analysis of synaptic ribbons may help identify its role in normal vision and in disease states.